Illegal Drugs Analysis by Thermal Desorption and Pyrolysis Combined with Direct Analysis in Real Time- Mass Spectrometry (TDP/DART-MS)
Hiroko Abe1, Chikako Takei2, Yasuo Shida2,3, Motoshi Sakakura4, Teruhisa Shiota4, Kayako Suga5, Daisuke Yajima1, Hirotaro Iwase1,6
of Chiba, 2BioChromato, Inc., 3University of Yamanashi, 4AMR, Inc., 5AB SCIEX, 6University of Tokyo
Table1 samples
Introduction
Drugs present in biological and autopsy specimens cannot be detected
without first selecting the pretreatment and the appropriate analytical
conditions for the drugs. Thus, it is extremely important to investigate the
analytical method suitable for specific compounds and samples. However,
in recent years the situation in which new substances appear one after
another, including New Psychoactive Substance (NPS) that threaten society,
it is very difficult to examine individually the analytical conditions that are
appropriate for each new substance. Thus, the comprehensive analysis
system for drugs that require minimal investigation of pretreatment and
analytical conditions are greatly desired.
So, we are investigating an analytical method for directly analyzing drugs in
blood and urine that does not require any pretreatment.
Methods and Samples
The samples were standard drugs mixture (Table 1), and drugs mixture
loaded blood and urine (i.e., blank blood and blank urine samples with
drugs mixture added).
Mass spectra were obtained by using a TripleTOF5600+ (SCIEX) Q-Tof
mass spectrometer combined with a DART ion source (IonSense LLC)
and an ionRocket Thermal Desorption and Pyrolysis (TDP) device
(BioChromato, Inc.). The ionRocket was mounted between the DART
ion source and the mass spectrometer. We conducted our study by
assessing whether drugs could be detected by using this analytical
system (Figure 1).
He
Sample name
5F-AEB
5F-CUMYL-PICA
Br-DRAGON FLY
4 acetoxy DMT
4 acetoxy DiPT
Elemental composition
C20H28FN3O3
C23H27FN2O
C13H12BrNO2
C14H18N2O2
C18H26N2O2
 Analysis by TPD/DART-MS
Mmi
377.21092
366.21019
293.00459
246.13628
302.19888
5μL of sample solutions were put into the POT (Figure2) and samples
were gradient heated by TDP device.
Results
 Analysis by DART-MS
At first, in order to determine the analysis condition, drugs standard were
analyzed by DART-MS. All samples were detected as the protonated ion.
Analytical condition
Ionization:
DART positive
Set temperature: 400 degree Celsius
Ionization gas: Helium
MS measuring method:
Information Dependent Acquisition method (IDA)
Mass range: m/z 100 - 1000
280℃
140℃
3
Time (min)
5
Drugs mixture in blood
10μg/mL
5F-AEB
CH3
F
CH3
O
H
5F-AEB
N
N
O
H3C
H
F
O
H
CH3
CH3
CH3
CH3
5F-AEB
4-acetoxy DiPT
N
O
N
N
Drugs mixture std.
100ng/mL
4-acetoxy DMT
Br-DRAGON FLY
N
CH3
N
CH3
DART
Ion source
MS
Br-DRAGON FLY
5F-CUMYL-PICA
O
O
4-acetoxy DMT
4-acetoxy DiPT
5F-CUMYL-PICA
Figure3 Temperature program of TDP device
N
O
H3C
5F-AEB
7
N
N
H
As for drugs mixture in blood, when we analyzed the blood samples that was
pretreated by using dispersive solid-phase extraction for removing phospholipid,
whereupon the intensity were dramatically improved (Figure5).
RT
F
O
As a results of drugs mixture standards, each drugs were separated and detected
through thermal gradient heating for all samples, and thermal desorption profiles
were highly reproducible for individual drugs. Moreover, this analysis system was
seemed to have the potential of quantitative analysis for drugs, as the drug’s ion
intensity were increased with increasing drugs concentrations in the samples
(Figure4).
Drugs mixture std.
10μg/mL
420℃
1
F
samples
Analytical condition
Temperature program:
Ambient temperature to 420 degree Celsius at a rate of 70 degree
Celsius / min(Figure3).
Ionization:
DART positive
Set temperature: 400 degree Celsius
Ionization gas: Helium
MS measuring method:
Information Dependent Acquisition method (IDA)
Mass range: m/z 100 - 1000
Temperature
1University
5F-CUMYL-PICA
Drugs mixture in blood
(Pretreated)
10μg/mL
4-acetoxy DMT
4-acetoxy DiPT
5F-CUMYL-PICA
Br-DRAGON FLY
O
H
NH2
H3C
Br
O
H
O
TDP device
Br-DRAGON FLY
NH2
H3C
Br
1μg/mL
O
CH3
CH3
Conclusion
O
O
H3C
O
N
H3C
O
N
CH3
N
H
CH3
N
H
 TPD/DART-MS, DART-MS combined with the thermal desorption and pyrolysis
device enabled to acquire a mass spectrum through thermal gradient heating.
4-acetoxy DMT
CH3
CH3
O
O
O
O
CH3
H3C
N
CH3
H3C
CH3
N
CH3
CH3
N
H
10μg/mL
CH3
N
H
4-acetoxy DiPT
Figure1 TDP/DART-MS system
Figure4 Extracted ion currentgram of 10μg/mL drugs mixture std. in MeOH,
blood and pretreated by using dispersive SPE for removing phospholipid
Figure2 MS spectra and MS/MS spectra of drugs standard
Figure4 Extracted ion currentgram of 100ng/mL, 1μg/mL and 10μg/mL
drugs mixture std. in MeOH
 Each drugs were separated and detected by using TDP/DART-MS.
 This analysis system was seemed to have the potential of quantitative analysis
for drugs.
64th ASMS Conference
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